The major objective of this project is to determine what factors control the sensitivity of various tissues and metabolic processes to growth hormone in young and aging animals. Previous research suggests that fetal and neonatal growth in man and most animals may occur largely independently of growth hormone. Furthermore, adult and aging animals seem to be relatively insensitive to the anabolic actions of growth hormone. The first part of this project is to determine the times of onset and decline in sensitivity to growth hormone of the following processes: amino acid uptake, and protein synthesis, in the diaphragm; hepatic protein and RNA synthesis; lipolysis and glucose utilization in adipose tissue; and production of serum somatomedin. Then various attempts will be made to ascertain what produces these changes in sensitivity. For example, does sensitivity appear when growth hormone is first able to bind to the tissue, when thyroid function is established, when growth hormone is first able to lower cyclic nucleotide levels in muscle, or when somatomedin first appears in the serum? Also, experiments will be done to see if sensitivity is lost when tissues produce antagonists to growth hormone or somatomedin, or when high affinity receptors disappear.